crossing96/oncoscreening huggingface dataset:
Functional POR A503V is associated with the risk of bladder cancer in a Chinese population.	Human cytochrome P450 oxidoreductase (POR) plays important roles in the metabolism of exogenous carcinogens and endogenous sterol hormones. However, few studies have explored the association between POR variants and the risk of bladder cancer. In this study, we first sequenced all 16 POR exons among 50 randomly selected controls, and found three variants, rs1135612, rs1057868 (A503V) and rs2228104, which were then assessed the relation to risk of bladder cancer in a case-control study of 1,050 bladder cancer cases and 1,404 cancer-free controls in a Chinese population. People with A503V TT genotype have a decreased risk of bladder cancer in a recessive model (TT vs. CC/CT, OR = 0.73, 95% CI = 0.57-0.93), which was more pronounced among elderly male, non-smoking, subjects. Especially, A503V TT genotype showed a protective effect in the invasive tumor stage. Functional analysis revealed that A503V activity decreased in cytochrome c reduction (50.5 units/mg vs. 135.4 units/mg), mitomycin C clearance (38.3% vs. 96.8%), and mitomycin C-induced colony formation (78.0 vs 34.3 colonies per dish). The results suggested that POR A503V might decrease the risk of bladder cancer by reducing its metabolic activity, and should be a potential biomarker for predicting the susceptibility to human bladder cancer.	bladder
Emmprin Expression Predicts Response and Survival following Cisplatin Containing Chemotherapy for Bladder Cancer: A Validation Study.	PURPOSE: Neoadjuvant chemotherapy before cystectomy is recommended. To our knowledge the subset of patients likely to benefit has not been identified. We validate emmprin and survivin as markers of chemotherapy response. MATERIALS AND METHODS: Tumor specimens were obtained before therapy from a total of 250 patients with T1-T4 bladder cancer enrolled in 2 randomized trials comparing neoadjuvant chemotherapy before cystectomy with a surgery only arm. Protein expression was determined by immunohistochemistry. RESULTS: Expression was categorized according to predefined cutoffs reported in the literature. Data were analyzed with the Kaplan-Meier method and Cox models. Patients in the chemotherapy cohort with negative emmprin expression had significantly higher down staging overall survival than those with positive expression (71% vs 38%, p<0.001). The values for cancer specific survival were 76% and 56%, respectively (p<0.027). In the cystectomy only cohort emmprin expression was not associated with overall survival (46% vs 35%, p=0.23) or cancer specific survival (55% vs 51%, p=0.64). Emmprin negative patients had an absolute risk reduction of 25% in overall survival (95% CI 11-40) and a number needed to treat of 4 (95% CI 2.5-9.3). Survivin expression was not useful as a biomarker in this study. Limitations were the retrospective design and heterogeneity coupled with the time difference between the trials. CONCLUSIONS: Patients with emmprin negative tumors have a better response to neoadjuvant chemotherapy before cystectomy than those with positive expression.	bladder
Ruptured Mycotic Aortic Aneurysm after Bacille Calmette-Guerin Therapy.	To report a case of a ruptured mycotic abdominal aortic aneurysm (MAA) after intravesical Bacille Calmette-Guerin (BCG) therapy because of bladder carcinoma. A 57-year-old male patient was admitted to our hospital for follow-up computed tomography 14 months after transurethral resection of a papillary carcinoma of the bladder and intravesical BCG therapy. The CT scan revealed a ruptured MAA aneurysm and the patient underwent an endovascular repair with an aorto-bi-iliac stent graft. A ruptured MAA is a rare but lethal complication after BCG instillation therapy. The standard therapy is the open reconstruction but according to the literature an endovascular therapy in combination with long-term antibiotics should be considered as a bridging or a definite solution.	bladder
Clear cell adenocarcinoma of the bladder with intravesical cervical invasion.	A 26-year-old woman with a complicated urological and gynecological history with uterine didelphys with bilaterally inserting intravesical cervical oses presented with cyclical haematuria. Work up revealed a mass in the ectopic cervical os and adjacent bladder wall. Subsequent resection confirmed a clear cell adenocarcinoma of urological origin with invasion into neighbouring os.	bladder
Small Cell Carcinoma of the Urinary Bladder: A Retrospective, Multicenter Rare Cancer Network Study of 107 Patients.	PURPOSE: Small cell carcinomas of the bladder (SCCB) account for fewer than 1% of all urinary bladder tumors. There is no consensus regarding the optimal treatment for SCCB. METHODS AND MATERIALS: Fifteen academic Rare Cancer Network medical centers contributed SCCB cases. The eligibility criteria were as follows: pure or mixed SCC; local, locoregional, and metastatic stages; and age ≥18 years. The overall survival (OS) and disease-free survival (DFS) were calculated from the date of diagnosis according to the Kaplan-Meier method. The log-rank and Wilcoxon tests were used to analyze survival as functions of clinical and therapeutic factors. RESULTS: The study included 107 patients (mean [±standard deviation, SD] age, 69.6 [±10.6] years; mean follow-up time, 4.4 years) with primary bladder SCC, with 66% of these patients having pure SCC. Seventy-two percent and 12% of the patients presented with T2-4N0M0 and T2-4N1-3M0 stages, respectively, and 16% presented with synchronous metastases. The most frequent curative treatments were radical surgery and chemotherapy, sequential chemotherapy and radiation therapy, and radical surgery alone. The median (interquartile range, IQR) OS and DFS times were 12.9 months (IQR, 7-32 months) and 9 months (IQR, 5-23 months), respectively. The metastatic, T2-4N0M0, and T2-4N1-3M0 groups differed significantly (P=.001) in terms of median OS and DFS. In a multivariate analysis, impaired creatinine clearance (OS and DFS), clinical stage (OS and DFS), a Karnofsky performance status <80 (OS), and pure SCC histology (OS) were independent and significant adverse prognostic factors. In the patients with nonmetastatic disease, the type of treatment (ie radical surgery with or without adjuvant chemotherapy vs conservative treatment) did not significantly influence OS or DFS (P=.7). CONCLUSIONS: The prognosis for SCCB remains poor. The finding that radical cystectomy did not influence DFS or OS in the patients with nonmetastatic disease suggests that conservative treatment is appropriate in this situation.	bladder
The effect of metformin on cancer-specific survival outcomes in diabetic patients undergoing radical cystectomy for urothelial carcinoma of the bladder.	PURPOSE: Metformin, a first-line oral therapy for diabetes, has anticancer properties. Our objective was to evaluate the association between metformin use and oncologic outcomes in diabetic patients undergoing radical cystectomy (RC) for bladder cancer (BC). METHODS: A single-institution retrospective cohort (January 1997-June 2013) of diabetic patients undergoing RC was assembled. Medication use was assessed at time of surgery. Outcome measures were recurrence-free survival (RFS), BC-specific survival (BCSS), and overall survival (OS). Multivariable Cox proportional hazards models were used. To create parsimonious models, the change of estimate approach (10% threshold) was used as a variable selection strategy for final model inclusion separately for each outcome measure. RESULTS: Of 421 patients, 85 (20%) had diabetes. There were 39 (46%) patients on metformin therapy. Among diabetic patients, there were 21 patients with BC recurrence, 16 who died of BC, and 30 who died overall. In univariate analyses, metformin use among diabetic patients was associated with improved RFS (hazard ratio = 0.54, 95% CI: 0.33-0.88, P = 0.013) and trended toward improved BCSS (hazard ratio = 0.65, 95% CI: 0.40-1.07, P = 0.087), but not with OS (P = 0.87). In multivariable models, metformin use among diabetic patients was associated with significantly improved RFS (adjusted hazard ratio = 0.38, 95% CI: 0.20-0.72, P = 0.003) and BCSS (adjusted hazard ratio = 0.57, 95% CI: 0.35-0.91, P = 0.019), but not with OS (P = 0.89). Use of other oral hypoglycemic agents or insulin was not associated with oncologic outcomes. CONCLUSIONS: Our study is among the first to report an association between metformin use and improved RFS and BCSS in diabetic patients undergoing RC. Given its low cost and demonstrated safety among nondiabetic patients, further studies are warranted to evaluate potential therapeutic and preventive roles of metformin in BC.	bladder
Patterns of Lymphatic Metastases in Upper Tract Urothelial Carcinoma and Proposed Dissection Templates.	PURPOSE: Information on patterns of lymph node metastases for upper tract urothelial carcinoma is sparse. We investigated patterns of lymph node metastases in upper tract urothelial carcinoma. MATERIALS AND METHODS: We performed a retrospective multi-institutional study of 73 patients with N+M0 upper tract urothelial carcinoma who underwent template lymphadenectomy during nephroureterectomy. Anatomical locations of tumor, and number of lymph nodes removed and positive lymph nodes were analyzed and descriptive statistics were performed. RESULTS: On the right side the 20 renal pelvis tumors had lymph node metastases to the hilum in 22.1% of cases, and to paracaval, retrocaval and interaortocaval regions in 44.1%, 10.3% and 20.6%, respectively. The 10 proximal ureter tumors had lymph node metastases to the hilum in 46.2% of cases, and to paracaval and retrocaval regions in 46.2% and 7.7%, respectively. The 2 distal ureter tumors had lymph node metastases equally to the paracaval and pelvic regions. On the left side the 24 renal pelvis tumors had lymph node metastases to the hilum region in 50.0% of cases and to the para-aortic region in 30.0%. The 8 proximal ureter tumors had lymph node metastases to the hilum region in 36.4% of cases and the para-aortic region in 63.6%. The 5 mid ureter tumors had lymph node metastases to the para-aortic, common iliac and internal iliac regions in 40%, 40% and 20% of cases, respectively. The 4 distal ureter tumors had lymph node metastases to the para-aortic, common iliac, external iliac and internal iliac regions in 33.3%, 33.3%, 16.7% and 16.7% of cases, respectively. Interaortocaval involvement from both sides as well as out of field lymph node metastases appeared to occur secondarily. Consolidated templates were constructed based on the available data. CONCLUSIONS: Upper tract urothelial carcinoma has characteristic patterns of lymph node metastases depending on the side and anatomical location of the primary tumor, including right-to-left migration and involvement of interaortocaval nodes in the setting of proximal disease. Standardized dissection templates should be prospectively evaluated in multicenter trials to assess morbidity and potential clinical benefit.	bladder
Urologic cancer in Indonesia.	Non-communicable diseases, including cancer, start to become more common in Indonesia. According to the government statement, incidence of malignant diseases increased annually up to 8% in the last decade and these diseases become the seventh leading cause of death in Indonesia. On the basis of the latest Globocan report on cancer incidence in Indonesia, prostate cancer ranks sixth; followed by bladder (12th) and kidney (18th). More than half of patients with kidney cancer are diagnosed in the advanced stage. Besides renal cell carcinoma, there are significant number of people affected with squamous cell and transitional cell carcinoma because of kidney stones. Radical nephrectomy or cytoreductive nephrectomy was the primary treatment, mostly done as an open procedure. Transitional cell carcinoma is the commonest histology type in bladder cancer cases followed by squamous cell carcinoma, which almost always related to bladder stones. Unfortunately, >70% of our cases were diagnosed with muscle invasive bladder cancer, and ∼60% of these patients refused further radical treatment. Incidence of prostate cancer is increasing rapidly and it becomes the third most common cancer in men. However, most of our patients are diagnosed in the advanced stage. Radical prostatectomy or external beam radiotherapy is the treatment of choice in localized disease. Nearly 40% of the elderly patients are treated with primary androgen deprivation therapy. Therefore, it requires more research by the Indonesian urologists and other healthcare providers to diagnose these cancers in earlier stage as well as community education for prevention.	bladder
[Neoadjuvant or Adjuvant Chemotherapy for Bladder Cancer?].	Advanced urothelial carcinoma of the bladder is associated with a high metastatic potential. Life expectancy for metastatic patients is poor and rarely exceeds more than one year without further therapy. Neoadjuvant chemotherapy can decrease the tumour burden while reducing the risk of death. Adjuvant chemotherapy has been discussed controversially. Patients with lymph node-positive metastases seem to benefit the most from adjuvant chemotherapy. In selected patients, metastasectomy can prolong survival. In metastastic patients, the combination of gemcitabine and cisplatin has become the new standard regimen due to a lower toxicity in comparison to the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). For second-line treatment, vinflunine is the only approved therapeutic agent.	bladder
[Influence of Comorbidity on Mortality and Morbidity in the Radical Cystectomy for Bladder Cancer].	Radical cystectomy (RC) with bilateral pelvic lymph node dissection constitutes the gold standard treatment for muscle-invasive and high-risk non-muscle-invasive urothelial carcinoma of the bladder refractory to instillation therapy. Although radical cystectomy is performed with curative intent, the overall 5-year survival has been reported to be as low as 62% in the current literature. Various clinico-pathological parameters determine post-RC outcome, but besides these, the role of comorbidity has gained increasing attention and can be quantified with various comorbidity scores. We here review the most recent data on comorbidity scores and performance indices, which have been assessed in patients, undergoing RC and highlight their clinical implications.	bladder
Complications following intravesical bacillus Calmette-Guerin treatment for bladder cancer: a case series of 22 patients.	BACKGROUND: Intravesical bacillus Calmette-Guerin (BCG) therapy is an effective and widely used treatment for superficial bladder carcinoma. Local complications are frequent whereas systemic complications are rare but can be serious, and their management is not well known. METHODS: We describe retrospectively the records of 22 patients treated in 3 infectious disease departments, for complications related to intravesical BCG therapy as treatment of bladder cancer. RESULTS: All the patients were male, with a median age of 68 years (range 56-88). Complications occurred after a median of 5 instillations (range 1-11) and were observed within 24 h following BCG instillation for 14 patients. Common symptoms were fever (n = 20), impaired general condition (n = 14), and shortness of breath (n = 7). Six patients had a systemic septic reaction leading to transfer into the intensive care unit for five of them. Lung infiltration was the most frequent presentation (n = 11). Mycobacterium bovis was isolated from only two patients, but histology showed the presence of a granuloma in nine patients. Antimycobacterial treatment was initialized in 17 patients; the outcome was favorable in 16 patients, with a median length of symptoms resolution of 22.5 days (range 5-425 days). Eleven patients received corticosteroids in addition to specific treatment and had a more rapid improvement. One patient died with disseminated BCGitis proved by biopsy. CONCLUSIONS: Complications following intravesical BCG therapy are rare but can be severe and fatal. Histology seems to be the method that contributes most in confirmation of the diagnosis. Antimycobacterial therapy is effective, and probably more efficient when combined with corticosteroids, but the regimen and duration of the treatment are not standardized.	bladder
The use of water-soluble mucoadhesive gels for the intravesical delivery of epirubicin to the bladder for the treatment of non-muscle-invasive bladder cancer.	OBJECTIVES: To develop an epirubicin-loaded, water-soluble mucoadhesive gels that have the correct rheological properties to facilitate their delivery into the bladder via a catheter, while allowing for their spread across the bladder wall with limited expansion of the bladder and increasing the retention of epirubicin in the bladder and flushing with urine. METHODS: Epirubicin-loaded hydroxyl ethyl cellulose (HEC) and hydroxy propyl methyl cellulose (HPMC) gels were manufactured and tested for their rheological properties. Their ability to be pushed through a catheter was also assessed as was their in-vitro drug release, spreading in a bladder and retention of epirubicin after flushing with simulated urine. KEY FINDINGS: Epirubicin drug release was viscosity-dependent. The 1 and 1.5% HEC gels and the 1, 1.5 and 2% HPMC gels had the correct viscosity to be administered through a model catheter and spread evenly across the bladder wall under the pressure of the detrusor muscle. The epirubicin-loaded gels had an increased retention time in the bladder when compared with a standard intravesical solution of epirubicin, even after successive flushes with simulated urine. CONCLUSION: The increased retention of epirubicin in the bladder by the HEC and HPMC gels warrant further investigation, using an in-vivo model, to assess their potential for use as treatment for non-muscle-invasive bladder cancer.	bladder
[Activity and efficacy of vinflunine in metastatic carcinoma of the bladder after failure of adjuvant treatment: description of a clinical case].	Vinflunine is the only drug tested in a phase III trial and, to date, approved for advanced or metastatic bladder cancer after failure of a prior platinum-containing regimen. We report a case of a man with metastatic bladder cancer treated with vinflunine after failure of an adjuvant chemotherapy with carboplatin and gemcitabine.	bladder
Management of muscle-invasive bladder cancer in the elderly.	PURPOSE OF REVIEW: The number of cases of muscle-invasive bladder cancer is increasing along with the age of the population. Management of muscle-invasive bladder cancer in the elderly is complex, requiring a multidisciplinary team approach and a comprehensive assessment of each individual patient. RECENT FINDINGS: A geriatric assessment should be used to inform treatment decisions in elderly patients with bladder cancer. There is increasing evidence to support aggressive therapy in appropriate elderly patients, including radical cystectomy and neoadjuvant chemotherapy. Adjuvant chemotherapy also has a role in patients with high-risk disease after cystectomy. A bladder preservation approach with trimodality therapy is a well tolerated and effective alternative to cystectomy in appropriately selected patients. SUMMARY: Treatment decisions should not be based on chronologic age alone and advanced age should not preclude aggressive or curative therapy. The recent molecular characterization of bladder cancer and several recent immunotherapy trials provide hope of a more targeted approach to treatment of bladder, potentially improving both effectiveness and tolerability of treatment regimens in the elderly.	bladder
Sarcomatoid urothelial carcinoma of the bladder: a contemporary clinicopathologic analysis of 37 cases.	INTRODUCTION: Sarcomatoid urothelial carcinoma is a dedifferentiated biphasic tumor that exhibits morphological and/or immunohistochemical evidence of epithelial and mesenchymal differentiation. In this series, we analyzed the clinicopathologic features of this rare variant of urothelial carcinoma. MATERIALS AND METHODS: A search was made through our surgical pathology files and consultation files of the senior author for cases of sarcomatoid urothelial carcinoma of the bladder from 2005-2014. All the slides were retrieved and re-reviewed, and clinical data was also obtained including follow up. RESULTS: Thirty-seven cases of sarcomatoid urothelial carcinoma of the bladder were identified. Mean patient age was 71 years (range: 51 to 88 years). Twenty-six of 37 (70%) patients were male and 11/37 (30%) patients were female. Twenty-five cases were from cystectomy/cystoprostatectomy specimens, 8 cases from transurethral resection of bladder tumor specimens and 4 cases were from biopsy specimens. The mean tumor size was 5 cm (range: 1.4 cm to 13.0 cm). Four of 37 (10%) cases had focal heterologous components; 1 case with both chondroid and osteoid, 2 cases with chondroid and 1 case rhabdoid elements. Twenty-one of 37 (56%) patients died within a year of presentation. CONCLUSIONS: Sarcomatoid urothelial carcinoma of the bladder is more prevalent in males, with the mean age of 71 years in our series. Smoking is an important risk factor. Sarcomatoid urothelial carcinoma is an aggressive variant of urothelial carcinoma which commonly presents at an advanced stage, and over 50% of patients in our series died of disease within 1 year of presentation.	bladder
Potent Apoptotic Response Induced by Chloroacetamidine Anthrathiophenediones in Bladder Cancer Cells.	We previously found that two neighboring G-quadruplexes behave as a molecular switch controlling the expression of HRAS (Cogoi, S.; Schekotikhin, A. E.; Xodo, L. E. Nucl. Acids Res. 2014, DOI: 10.1093/nar/gku574). In this study we have designed anthrathiophenediones with two chloroacetamidine-containing side chains (CATDs) as G-quadruplex binders and have examined their anticancer activity in T24 bladder cancer cells bearing mutant HRAS and in T24 xenografts. The designed CATDs (3a-e), bearing alkyl side chains of different length, penetrate T24 cancer cells more than their analogues with guanidine-containing side chains. The lead compounds 3a and 3c inhibit HRAS expression, metabolic activity, and colony formation in T24 cancer cells. They also activate a strong apoptotic response, as indicated by PARP-1, caspases 3/7, and annexin V/propidium iodide assays. Apoptosis occurs under conditions where cyclin D1 is down-regulated and the cell cycle arrested in G2 phase. Finally, compound 3a inhibits the growth of T24 xenografts and increases the median survival time of nude mice.	bladder